The short term objectives of this proposal are: (i) to determine the magnitude of sexual dimorphism in vascular tissue of the coronary, pulmonary and systemic circulations as indicated by measurements of sensitivity and contractility to vasoactive agonists: (ii) to establish the quantitative and qualitative contributions by the products of the prostaglandin cyclooxygenase pathway in the expression of sexual dimorphism in the same models; (iii) to define the nature of the relationship between calcium/calmodulin and the prostaglandin systems in mediating sexual dimorphism in the same models; (iv) to evaluate the contribution of vascular prostaglandin receptors to the responsivity of tissues to vasoactive agonists; and (v) to relate all the above to the gonadal steroid milieu in which the vasculature normally functions during the life of the animal. The long term objectives are to relate the phenomenon of sexual dimorphism in vascular tissues to gender differences in various cardiovascular syndromes and diseases and, thereby, to provide a rationale for the application of new ideas and approaches to the prevention and treatment of these pathologic conditions. The implication of the prostaglandin system in therapeutics is particularly important because many available drugs may be brought to bear in the management of known cardiovascular disorders. The proposal is based on our findings that males and testosterone-treated animals have a greater platelet aggregability, thrombosis formation, and blood vessel sensitivity and contractility than do females. Anti-androgens or prostaglandin synthetase inhibitors preferentially protect the male. By studying the physiology and pharmacology of blood vessels and relating this to prostaglandins and calcium regulation, we hope to discover the basis for this sex difference and the androgen effect.